Caffeine Citrate in Preterm Infants at Risk of Apnea in Zambia

The University of Alabama at Birmingham

Status and phase: Begins enrollment this month; Phase 4

Conditions: Premature Infant Disease; Apnea of Prematurity; Development, Infant

Treatments: Drug: Placebo-Sterile water 1ml/kg/day; Drug: Caffeine citrate 20mg/kg/day

Study type: Interventional

Funder types: Other

Identifiers

NCT06518603

UAB-300013205

000533428-0004 (Other Identifier)

UAB Dixon End Chair/3102800 (Other Identifier)

Details and patient eligibility

About

The goal of this clinical trial is to learn if caffeine citrate prevents apneic events that result in sick visits in moderately preterm infants after discharge from the hospital. It will also learn if the use of caffeine leads to better developmental outcomes at 12 months of age.

Our research questions are:

1. Does continued treatment of moderately preterm newborns with caffeine citrate after hospital discharge prevent or decrease apneic events that result in sick visits?
2. Will the continued use of caffeine citrate lead to improved developmental outcomes among infants at 12 months of age?

Researchers will compare caffeine citrate to a placebo (a look-alike substance that contains no drug) to see if caffeine citrate prevents apneic spells which result in healthcare visits.

Parents of participants will:

1. Administer caffeine citrate 20mg/kg/day or a placebo (equivalent volume of sterile water) orally every day for up to 28 days after hospital discharge

2. Keep a diary of symptoms and any apneic events

3. Check in with researchers via telephone call once a week

4. Return to clinic for infant physical examination at 28 days

5. Return to the clinic for infant physical examination at 2 months

6. Return to clinic for infant neurodevelopmental examination with Ages and Stages Questionnaire at 12 months of age

Full description

Once an infant has been deemed stable by the neonatologist and the neonatologist recommends discontinuing treatment for apnea of prematurity 5 days before hospital discharge as per standard of care, the parent/guardian will be approached for consent. Following consent, study participants will be randomized to either the Intervention Arm (20mg/kg/day caffeine citrate; 2mg/ml) dose and equal volume of placebo (sterile water) using trial-specific single dose caffeine/placebo vials. Upon the study participant's hospital discharge, the pharmacist will prepare the caffeine citrate and placebo relevant to the weight of the infant within 48 hours prior to discharge. The doses will not be adjusted for weight gain after discharge. Caffeine levels will not be checked routinely and checking levels will be discouraged to optimize masking.

While at the hospital, infants will receive the oral dose from government staff. Following hospital discharge, the parent/guardian will be given enough doses of caffeine or equivalent placebo for 28 days and will be asked to administer it to their infant orally daily, at the same time, until day 28. Unlike the intervention arm, all study participants randomized to the control arm (placebo) will discontinue receiving caffeine and will begin receiving placebo (sterile water) in the same volume orally as those in the intervention arm. The parent/guardian will also be given a booklet to register any apneic spells. The study RA will contact the parent/guardian on a weekly basis, up to day 28 and once at 2 months after hospital discharge for patient clinical monitoring and follow-up purposes.

Upon completion of the study at 12 months of life, all study participants will return to the hospital for neurodevelopmental screening using the Ages and Stages-3 Questionnaire for 12 months.

Data will be collected onto paper forms, which will then be entered into a REDCap Database, housed at the Centre for Infectious Disease Research in Zambia (CIDRZ) offices. Data forms will be kept in locked cabinets, retained and destroyed per incineration after 5 years. Access to the data forms and REDCap Database will be restricted to those with a need to know.

Enrollment: 340 estimated patients

Sex: All

Ages: Under 12 months old

Volunteers: No Healthy Volunteers

Inclusion criteria

Newborns:

1. 29 0/7 to 33 6/7 weeks GA (or with a birth weight 1.0 to 2.0 kg if pregnancy dating is unreliable) admitted to the UTH NICU,
2. On methylxanthines with plans to discontinue on methylxanthine,
3. Off oxygen therapy for >48 hours at the time of evaluation for eligibility,
4. Receiving full daily feeds,
5. Deemed stable and ready to go off caffeine as recommended by the Neonatologist
6. 18+ years of age (parent)

Exclusion criteria

1. Newborns with neuromuscular conditions affecting respiration,
2. Major congenital malformations and genetic disorders,
3. Unable to obtain parental or guardian consent

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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340 participants in 2 patient groups, including a placebo group

Oral Caffeine Citrate 20mg/kg/day

Experimental group

Description:

Caffeine Citrate 20 mg/kg/day given orally once a day for 28 days. (2mg/ml)

Treatment:

Drug: Caffeine citrate 20mg/kg/day

Placebo

Placebo Comparator group

Description:

Sterile water 1ml/kg/day given orally once a day for 28 days.

Treatment:

Drug: Placebo-Sterile water 1ml/kg/day